This project has attempted to apply our understanding of the cellular mechanisms involved in in vitro anti-MHC responses to in vivo transplantation responses. In studying skin allograft rejection, we have identified the phenotype, specificity, and interaction capabilities of the T cells able to initiate and effect in vivo rejection responses. Using allophenic skin grafts, we found that the effector mechanism of skin graft rejection is itself antigen-specific, and that defects in Th cell function result in longterm retention of skin allografts despite the presence of antigen-specific effector cells. In addition, we have assessed the cellular mechanisms mediating the rejection of fetal pancreas and Islet cell allografts.